GENOME-WIDE SCREEN OF GENES THAT REGULATE LIPID DROPLET DYNAMICS IN SACCHAROMYCES CEREVISIAE

Ph.DDOCTOR OF PHILOSOPH

Nonlinear system identification and control using state transition algorithm

By transforming identification and control for nonlinear system into optimization problems, a novel optimization method named state transition algorithm (STA) is introduced to solve the problems. In the proposed STA, a solution to a optimization problem is considered as a state, and the updating of a solution equates to a state transition, which makes it easy to understand and convenient to implement. First, the STA is applied to identify the optimal parameters of the estimated system with previously known structure. With the accurate estimated model, an off-line PID controller is then designed optimally by using the STA as well. Experimental results have demonstrated the validity of the methodology, and comparisons to STA with other optimization algorithms have testified that STA is a promising alternative method for system identification and control due to its stronger search ability, faster convergence rate and more stable performance.Comment: 20 pages, 18 figure

A Robust and Powerful Set-Valued Approach to Rare Variant Association Analyses of Secondary Traits in Case-Control Sequencing Studies

In many case-control designs of genome-wide association (GWAS) or next generation sequencing (NGS) studies, extensive data on secondary traits that may correlate and share the common genetic variants with the primary disease are available. Investigating these secondary traits can provide critical insights into the disease etiology or pathology, and enhance the GWAS or NGS results. Methods based on logistic regression (LG) were developed for this purpose. However, for the identification of rare variants (RVs), certain inadequacies in the LG models and algorithmic instability can cause severely inflated type I error, and significant loss of power, when the two traits are correlated and the RV is associated with the disease, especially at stringent significance levels. To address this issue, we propose a novel set-valued (SV) method that models a binary trait by dichotomization of an underlying continuous variable, and incorporate this into the genetic association model as a critical component. Extensive simulations and an analysis of seven secondary traits in a GWAS of benign ethnic neutropenia show that the SV method consistently controls type I error well at stringent significance levels, has larger power than the LG-based methods, and is robust in performance to effect pattern of the genetic variant (risk or protective), rare or common variants, rare or common diseases, and trait distributions. Because of the SV method’s striking and profound advantage, we strongly recommend the SV method be employed instead of the LG-based methods for secondary traits analyses in case-control sequencing studies

Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast

Lipid droplets (LDs) are emerging cellular organelles that are of crucial importance in cell biology and human diseases. In this study, we present our screen of ∼4,700 Saccharomyces cerevisiae mutants for abnormalities in the number and morphology of LDs; we identify 17 fld (few LDs) and 116 mld (many LDs) mutants. One of the fld mutants (fld1) is caused by the deletion of YLR404W, a previously uncharacterized open reading frame. Cells lacking FLD1 contain strikingly enlarged (supersized) LDs, and LDs from fld1Δ cells demonstrate significantly enhanced fusion activities both in vivo and in vitro. Interestingly, the expression of human seipin, whose mutant forms are associated with Berardinelli-Seip congenital lipodystrophy and motoneuron disorders, rescues LD-associated defects in fld1Δ cells. Lipid profiling reveals alterations in acyl chain compositions of major phospholipids in fld1Δ cells. These results suggest that an evolutionally conserved function of seipin in phospholipid metabolism and LD formation may be functionally important in human adipogenesis

Effect of Grain Coalescence on Dislocation and Stress Evolution of GaN Films Grown on Nanoscale Patterned Sapphire Substrates

Two types of nucleation layers (NLs), including in-situ low-temperature grown GaN (LT-GaN) and ex-situ sputtered physical vapor deposition AlN (PVD-AlN), are applied on cone-shaped nanoscale patterned sapphire substrate (NPSS). The initial growth process of GaN on these two NLs is comparably investigated by a series of growth interruptions. The coalescence process of GaN grains is modulated by adjusting the three-dimensional (3D) temperatures. The results indicate that higher 3D temperatures reduce the edge dislocation density while increasing the residual compressive stress in GaN films. Compared to the LT-GaN NLs, the PVD-AlN NLs effectively resist Ostwald ripening and facilitate the uniform growth of GaN grains on NPSS. Furthermore, GaN films grown on NPSS with PVD-AlN NLs exhibit a reduction of over 50% in both screw and edge dislocation densities compared to those grown on LT-GaN NLs. Additionally, PVD-AlN NLs result in an increase of about 0.5 GPa in the residual compressive stress observed in GaN films

Fluid mud induced by periodic tidal advection and fine-grained sediment settling in the Yangtze estuary

This study presents in-situ observations of fluid mud in the Yangtze Estuary via a bottom tripod. Six occurrences of periodic fluid muds (F1-F6) were observed at high slack water, with suspended sediment concentration (SSC) exceeding 10 kg/m3. The thickness of the fluid mud varied across the six occurrences, reaching a maximum of 0.32m. Notably, temperature and salinity anomalies were observed within the fluid mud. The formation of fluid mud was found to be influenced by turbulence, with turbulence kinetic energy (TKE) below 5×10-4 m2/s2 favoring settling as the primary cause of formation. The critical shear stress (τcw) for fluid mud formation was estimated to be approximately 0.09 Pa. The formation of fluid muds during early tidal cycles was attributed to liquefaction and bed erosion resulting from strong waves. However, in most cases, the wave energy was insufficient for erosion, suggesting that advection played a role in sediment supply during the subsequent tide cycles. The increased cross-channel current velocity during flood facilitated the lateral transport of a significant amount of eroded sediment from shallow water into the channel. Due to its short duration, the fluid mud layer was entrained by the current before consolidation. Enhanced turbulence led to the breakdown of fluid mud at the early ebb. The critical τcw for fluid mud breakdown depended on the density and duration of the fluid mud, with a maximum value of up to 0.70 Pa. The absence of the fluid mud layer during low slack water and neap tide was associated with a reduction in advection and tidal pumping, disrupting the original sediment balance between supply and demand. These data provide valuable insights into the formation and breakdown of fluid mud, contributing to estuarine hydrodynamic modeling studies and enhancing the understanding of estuary dynamics

Plasmon-phonon coupling in large-area graphene dot and antidot arrays

Nanostructured graphene on SiO2 substrates pave the way for enhanced light-matter interactions and explorations of strong plasmon-phonon hybridization in the mid-infrared regime. Unprecedented large-area graphene nanodot and antidot optical arrays are fabricated by nanosphere lithography, with structural control down to the sub-100 nanometer regime. The interaction between graphene plasmon modes and the substrate phonons is experimentally demonstrated and structural control is used to map out the hybridization of plasmons and phonons, showing coupling energies of the order 20 meV. Our findings are further supported by theoretical calculations and numerical simulations.Comment: 7 pages including 6 figures. Supporting information is available upon request to author

Overexpression of the homoterpene synthase gene, OsCYP92C21, increases emissions of volatiles mediating tritrophic interactions in rice

Plant defense homoterpenes can be used to attract pest natural enemies. However, the biosynthetic pathway of homoterpenes is still unknown in rice, and the practical application of such indirect defense systems suffers from inherent limitations due to their low emissions from plants. Here, we demonstrated that the protein OsCYP92C21 is responsible for homoterpene biosynthesis in rice. We also revealed that the ability of rice to produce homoterpenes is dependent on the subcellular precursor pools. By increasing the precursor pools through specifically subcellular targeting expression, genetic transformation and genetic introgression, we significantly enhanced homoterpene biosynthesis in rice. The final introgressed GM rice plants exhibited higher homoterpene emissions than the wild type rice and the highest homoterpene emission reported so far for such GM plants even without the induction of herbivore attack. As a result, these GM rice plants demonstrated strong attractiveness to the parasitic wasp Cotesia chilonis. This study discovered the homoterpene biosynthesis pathway in rice, and lays the foundation for the utilization of plant indirect defense mechanism in the “push‐pull” strategy of integrated pest management through increasing precursor pools in the subcellular compartments and overexpressing homoterpene synthase by genetic transformation